Wk 4 - Nucleic Acid Inhibitors

Question 1

Rifamycins:

Rifampin and Fidoxamicin

Answer 1

• Bactericidal
• Inhibit RNA polymerase

Mechanism of Inhibition:
Bind bacterial RNA pol and block mRNA elongation

Spectrum of activity:
Rifampin - TB and extended combination use
Fidoxamicin - Gram + anaerobes

Mechanism of resistance:
Rifampin -
Intrinsic: drug can’t bind RNA pol subunit
Acquired: mutated rpoB gene (drug can’t bind)
Fidoxamicin -
Pt mutation in RNA pol (in vitro only)

Adverse effects:
Rifampin
∆ cytochrome P450 enzyme… medication will be metabolized at a higher rate
Deacetylate Rifampin makes it more excreted from body

Question 2

Fluoroquinolones:

Ciprofloxacin, levofloxacin, moxifloxacin

Answer 2

• Bactericidal
• Inhibit DNA replication

Mechanism of inhibition:
- Gram +: bind topo IV and stop stabilization that happens during separation of cells
- Gram -: bind topo II and stop supercoiling relaxation
THIS CAUSES dsDNA strand breaks

Spectrum of activity:

• Broad (gram + and -)
• Can target mycoplasma (no cell wall at all!)

Mechanism of resistance:

• Efflux pumps
• Mutated topoisomerases

Adverse effects:

• GI issues
• C. diff colitis and candida vaginitis
• DON’T TAKE IF PREGNANT/BREASTFEEDING!
• Avoid metals – cause decreased absorption of drug

Question 3

What are the Rifamycins

Answer 3

Rifampin and Fidoxamicin

Question 4

What are the Fluoroquinolones

Answer 4

Ciprofloxacin, levofloxacin, moxifloxacin

Question 5

Sulfonamides and Trimethoprim

- Sulfamethoxazole and trimethoprim

Answer 5

• Bacteriostatic if alone - BACTERICIDAL IF COMBINED AS BACTRIN
• Folate antagonists

Mechanism of inhibition:

• Sulfamethoxazole: competitive inhibitor of dihydropteroate synthase
• Trimethoprim: inhibits dihydrofolate reductase

Mechanism of resistance:

• ∆ enzyme shape
• Efflux pumps
• Don’t use folate metabolism

Adverse effects:

• Hypersensitivity/rash with sulfamethoxazole because of sulfur moiety (avoid other drugs with this moiety)
• Renal failure from crystalluria
• Hemolysis if G6P dehydrogenase sucks
• Newborns: kernicterus - drug binds albumin and causes free bilirubin levels to crazy increase

Question 6

What do Rifampin and Fidoxamicin do

Answer 6

Inhibit RNA polymerase

Question 7

What does Cipro, levofloxacin, and moxifloxacin do?

Answer 7

Inhibit DNA replication

Inhibit Topoisomerases II and IV

Question 8

What do Sulfonamides/Trimethoprim do?

Answer 8

Inhibit folate metabolism

Question 9

Bactrin

Answer 9

Sulfamethoxazole and trimethoprim combined

• Blocks folate synthesis pathway

Question 10

Metronidazole

Answer 10

• Bactericidal

Mechanism of inhibition:
- Drug is reduced and acts as e– sink that develops into free radicals –> cell death

Spectrum of Activity:

• Anaerobic bacteria (C. diff too)
• Protozoa

Mechanism of Resistance:
- None

Adverse effects:

• GI issues
• Metallic taste
• Headache
• DON’T TAKE DURING PREGNANCY!
• DON’T DRINK! – Disulfiram reaction

Question 11

Nitrofurantoin

Answer 11

• Bactericidal

Mechanism of inhibition:

• Reduced by bacterial flavoproteins – intermediates activated!
• Intermediates ∆/inactivate ribosomal proteins to STOP SYNTHESIS OF DNA!

Spectrum of activity:
- Broad spectrum for UTIs
(gets secreted fast in the active form)

Mechanism of resistance:
- None

Adverse effects:

• Vomiting
• Rash

Question 12

Which drugs can do a disulfiram reaction?

Answer 12

Metronidazole and 2nd generation cephalosporins

Question 13

Which drugs should you prescribe with UTI?

Answer 13

• Nitrofurantoin
• Bactrin

… Probably E. coli :(